I propose to study the various control elements that govern regulation of the histidine biosynthetic enzymes in the yeast Saccharomyces cerevisiae. Both a genetic and biochemical approach is planned. A series of different selection procedures will be used to obtain different classes of regulatory mutations: mutations which prevent or cause derepression; mutations involved in a general control system for many amino acid biosynthetic pathways, and mutations specific for histidine regulation; mutations which are linked or unlinked to the structural genes they control; mutations at DNA sites and in structural genes; and mutations in positive and negative regulatory elements. All of these mutations will be thoroughly analyzed for their genetic properties and regulatory functions. Interactions among the different elements and sites will be studied. Experiments will also be undertaken to elucidate the role of a yeast transposable element which we have generated which carries the his 4 gene. The mechanism of insertion and excision will be explored. I also propose to isolate the specific his 4 DNA and his 4mRNA for studies of his4 gene regulation and the his4 transposable element.